David Ludwig, MD, PhD, an endocrinologist at Boston Children’s Hospital, has written popular books espousing a low-glycemic, low-carbohydrate diet for weight control. He has argued that high-glycemic diets are contributing to the epidemic of type 2 diabetes. But he hadn’t given much thought to carbohydrate restriction for type 1 diabetes until 2016.

At a conference, Ludwig met a surgeon with type 1 diabetes who maintains normal hemoglobin A1c levels (indicating high blood sugar control) on a very-low-carbohydrate diet. This surprised and impressed him: he had never seen any patient with type 1 diabetes able to completely normalize their hemoglobin A1cs. Moreover, most diabetes experts discourage very-low-carb diets, believing they pose a risk for hypoglycemia, or a dangerous drop in blood sugar. …

Many people who have Roux-en-Y gastric bypass surgery for obesity experience a striking but welcome side effect. In up to 80 percent of patients who also have type 2 diabetes, the diabetes abates even before they lose weight. A new study helps explain why, and suggests possible ways to combat diabetes (and obesity) without having to actually perform bariatric surgery.

“Our aim is to ‘reverse engineer’ the surgery, to find how it works and apply the mechanisms to new, less invasive treatments,” said study lead author Margaret Stefater, MD, PhD, a fellow in the lab of Nicholas Stylopoulos, MD, in a press release.

In type 1 diabetes, autoreactive T-cells (like the one in yellow) attack insulin-producing beta cells in the pancreas. What if blood stem cells could be taught to neutralize them? (Image: Andrea Panigada)

Type 1 diabetes is caused by an immune attack on the pancreatic beta cells that produce insulin. To curb the attack, some researchers have tried rebooting patients’ immune systems with an autologous bone-marrow transplant, infusing them with their own blood stem cells. But this method has had only partial success.

“We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease,” says Paolo Fiorina, MD, PhD, of Boston Children’s Hospital, senior investigator on the study.

But they also found that the defect can be fixed — by pre-treating the blood stem cells with small molecules or with gene therapy, to get them to make more of a protein called PD-L1.

In experiments, the treated stem cells homed to the pancreas and reversed hyperglycemia in diabetic mice, curing almost all of them of diabetes in the short term. One third maintained normal blood sugar levels for the duration of their lives. …

New research reveals why treatment might appear to fail to control glucose levels in many people with Type 2 diabetes: not taking their medication as prescribed.

“When patients have poor glycemic control, their physicians may assume that there was a medication failure when they were, in fact, not filling their prescriptions,” says Ken Mandl, MD, MPH, of Boston Children’s Hospital, the senior author of a new report in Diabetes Care.

The study raises the question of whether the same might be true for patients with other conditions. …

Autoimmune disease is usually treated using general immunosuppressants. But this non-targeted therapy leaves the body more susceptible to infection and other life-threatening diseases.

Now, scientists at Boston Children’s Hospital, the Massachusetts Institute of Technology (MIT) and the Whitehead Institute for Biomedical Research think they may have found a targeted way to protect the body from autoimmune disease. Their approach, published in Proceedings of the National Academy of Sciences, uses transfusions of engineered red blood cells to re-train the immune system. Early experiments in mice have already shown that the approach can prevent — and even reverse — clinical signs of two autoimmune diseases: a multiple-sclerosis (MS)-like condition and Type 1 diabetes. …

The yellow-green cells in this “mini-stomach” are capable of making insulin. The mini-organ was made from biopsied cells from mouse stomachs, with reprogramming factors added.

If only there were a cure. David Breault, MD, PhD, associate chief of the Division of Endocrinology at Boston Children’s Hospital, was seeing patient after patient with Type I diabetes. Children facing lifetimes of insulin injections, special diets and the threat of long-term complications including blindness, heart disease and kidney failure.

Breault knew that patients with type I diabetes mysteriously destroy their own insulin-producing beta cells. He had read reports of researchers transplanting beta cells to supplement insulin. These transplants, even when successful, required powerful immunosuppressant medications to prevent patients’ immune systems from attacking the donor cells.

But Breault was also aware that investigators had, for a decade, been looking to stem cells as the source of a constantly renewing supply of beta cells. Advancing that promise, he has now found a way to convert patients’ own cells — from the stomach and intestine — into beta cells that produce insulin. …

Blood-brain barrier on chip

(Wyss Institute at Harvard University)

The blood-brain barrier protects the brain against potentially damaging molecules, but its gate-keeping can also prevent helpful drugs from getting into the central nervous system. Reporting in PLoS One, a team at the Wyss Institute for Biologically Inspired Engineering describes a 3-D blood-brain barrier on a chip — a hollow blood vessel lined with living human endothelial cells and surrounded by a collagen matrix bearing human pericytes and astrocytes. …

Blood levels of the hormone IGFBP3 (enterostaminine), shown here in green, are markedly elevated in people with longstanding type 1 diabetes and launch a lethal attack on intestinal stem cells. Adding a protein that soaks up the excess hormone restores normal stem cell function and could help prevent or treat diabetic enteropathy. (All images by Riseon)

Up to 80 percent of people with long-standing type 1 diabetes develop gastrointestinal symptoms—abdominal pain, bloating, nausea, vomiting, diarrhea, constipation and fecal incontinence—that severely diminish quality of life. Recent evidence suggests that this condition, known as diabetic enteropathy, results from damage to the intestinal lining, but the details beyond that have been unclear.

A study in this week’s Cell Stem Cell, led by Paolo Fiorina, MD, PhD, now provides some answers. It demonstrates how diabetes can lead to destruction of the stem cells that maintain the intestinal lining, and identifies a potential drug that could protect these stem cells and prevent or treat diabetic enteropathy. …

Why don’t these wounds close? Blame a perfect storm of diabetic complications, such as reduced blood flow, neuropathy and impaired signaling between cells. According to research by Denisa Wagner, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, a poorly understood feature of our immune system’s neutrophils may be one more ingredient in the storm.